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Cytotoxic T lymphocyte count and survival time in women with metastatic breast cancer.

While prognostic factors in early stage breast cancer are well documented, few studies have examined predictors of the rate of metastatic progression. The purpose of this study was to examine cytotoxic T-cell lymphocyte (CTL) count as a marker of disease status in women with metastatic breast cancer. This study examined CTL subset counts as predictors of subsequent survival in 113 women with metastatic or recurrent breast cancer. Samples were measured by flow cytometry using monoclonal antibodies for cell surface antigens for percentages and absolute numbers of CTLs (CD3/CD8), total lymphocytes, T cells (CD3), helper T cells (CD3/CD4), and total white blood cell (TWC) count. Higher CTL counts emerged as a significant predictor of longer survival up to 7 years later (Wald = 7.40, p = 0.007; Cox regression model). The relationship of higher CTL count with enhanced survival was independent of the effects of medical treatment. CTLs were significantly associated with TWC count (r = 0.42, p < 0.001). However, TWC count was not associated with subsequent survival time. Higher CTL count was associated with Karnofsky performance status (r = 0.27, p = 0.004). However, after adjustment for the Karnofsky score, the CTL count/survival relationship remained significant (Wald = 4.33, p = 0.038). In conclusion, there is a robust relationship between CTL count and survival that is independent of the effects of medical treatments, TWC count, and Karnofsky performance status. Moreover, a reduced CTL count may be a mediator or marker of more rapid disease progression in metastatic breast cancer.

Adult↗

[1,25-Dihydroxyvitamin D3 receptors in lymphocytes and T- and B-lymphocyte count in patients with glomerulonephritis].

Content of receptors to hormonal form of vitamin D3, 1.25(OH)2D3, constituted 27.3 fmole/mg of protein in lymphocytes of peripheric blood of children with glomerulonephritis. In the patients concentration of total and ionized form of Ca2+ was decreased down to 2.04 mmole/L and 1.09 mmole/L, respectively, while an increase in parathormone (PTH) by 36% and a distinct decrease in 25(OH)D concentration (lower than 1.25 ng/ml) was found in blood; content of cAMP was also decreased in lymphocytes by 33%. At the same time, total content of T lymphocytes was decreased 1.5-fold in peripheric blood. Treatment with I-hydroxyvitamin D3 (1-1.5 mg daily, within 4 weeks) led to normalization of total and ionized form of Ca2+ and of 25(OH)D, but did not affect the PTH content in blood. Concentration of the receptors to 1.25(OH)2D3 was elevated up to 39.7 fmole/mg after I week of the treatment, whereas it was decreased to the initial level 24.8 fmole/mg within 4 weeks; simultaneous alteration in the cAMP content was observed in lymphocytes. Treatment with 1-(OH)D3 normalized also the T lymphocytes content in peripheric blood. The data obtained suggest that under conditions of glomerulonephritis only high content of receptors to 1.25(OH)2D3 in lymphocytes enabled to perform the cell response to the hormone effect.

B-Lymphocytes↗

[Change in rabbit blood lymphocyte count after repeated extracorporeal irradiation with cesium 137. Comparison of heparin and acenocoumarol effects].

During repetitive extracorporeal irradiation, heparin treatment is responsible for a very high lymphocytic peak which does not last more than two days. This peak is not observed after using acenocoumarol as anticoagulant. That is why the degree of lymphocyte depletion after RECIB is to be interpreted in function of the anticoagulant used. This peak is temporary. No matter the anticoagulant used, lymphopenia is obtained after 15 days. The level of lymphocytic depletion is independent of the initial lymphocytosis.

Acenocoumarol↗

Alefacept-induced decreases in circulating blood lymphocyte counts correlate with clinical response in patients with chronic plaque psoriasis.

This international, double-blind study examined the effects of alefacept on circulating lymphocytes in 507 patients with chronic plaque psoriasis, and determined whether these effects were related to clinical improvement. Patients were randomized to intramuscular placebo, alefacept 10 mg, or alefacept 15 mg once weekly for 12 weeks followed by 12 weeks of observation. Alefacept dose-dependently reduced CD4+ and CD8+ memory T cells, while sparing the na ve population. The greatest reductions in disease activity occurred in patients with the largest decreases in memory T cells. For example, a 50 % reduction from baseline Psoriasis Area Severity Index at any time during treatment or follow-up was observed in 66 % of patients who had the greatest reductions in CD4+ memory T cells versus in 40 % of patients who had the smallest reductions in this T-cell subset. These results provide further support for the deleterious roles of CD4+ and CD8+ memory T-cell subpopulations in psoriasis pathogenesis.

Alefacept↗

Relationship between antibody-dependent cellular cytotoxicity, plasma HIV type 1 RNA, and CD4+ lymphocyte count.

To explore the role of antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV-1 infection, ADCC was compared with plasma RNA and CD4+ cell count in 40 patients not receiving antiretroviral therapy and in seven patients after the initiation of treatment. Among untreated patients, ADCC effector cell function of peripheral blood mononuclear cells, measured by (51)Cr release assay, correlated inversely with viral load (R = -0.42, p = 0.007) and directly with CD4+ cell count (R = 0.52, p = 0.001). On the other hand, HIV-1-specific ADCC antibody level correlated directly with viral load, but only among patients with high CD4+ cell counts. Therapy-induced changes in ADCC effector cell function correlated strongly with changes in CD4+ cell count (R = 0.86, p = 0.014), whereas there was no consistent pattern of change in ADCC antibody with therapy. In a novel assay, ADCC reduced virus yield from CD4+ lymphocytes infected with a primary HIV isolate. ADCC may contribute to control of viremia, and CD4+ lymphocytes likely play a role in ADCC effector and antibody functions.

Anti-HIV Agents↗

Effect of clinical events on plasma HIV-1 RNA levels in persons with CD4+ T-lymphocyte counts of more than 500 x 10(6) cells/l.

OBJECTIVE: Immune stimulation of CD4 lymphocytes is thought to enhance HIV-1 replication in vivo. Therefore, we sought to define the impact of clinical events identified as putative immune activators on the variability of plasma HIV-1 RNA levels in persons with CD4 cell counts greater than 500 x 10(6) cells/l. DESIGN: We prospectively recorded clinical events and measured plasma HIV-1 RNA levels weekly for 24 weeks in 16 HIV-1-infected adults who were not receiving antiretroviral therapy and who had CD4 cell counts greater than 500 x 10(6) cells/l. METHODS: Standard weekly interviews were conducted to capture potential immune activators (e.g., infections, immunizations, and allergic reactions). All plasma HIV-1 RNA levels were measured using the Amplicor HIV-1 Monitor assay (Roche Diagnostics, Branchburg, New Jersey, USA) according to the manufacturer's instructions. RESULTS: Participants had remarkably stable viral loads during the 6 month study period. Infections were significantly more frequent during the 7 days prior to individual HIV-1 RNA measurements that exceeded the assay variation thresholds determined for this study (+/- 0.324 log) than during the comparable time periods preceding stable measurements (P = 0.023). As a group, the eight participants who had one to four HIV-1 RNA measurements that exceeded the thresholds experienced more infections and declining CD4 cell counts over the study course compared to the eight participants whose measurements all fell within the thresholds (P = 0.058 and 0.053 respectively). CONCLUSIONS: Our study suggests that in untreated HIV-1-infected persons with CD4 cell count greater than 500 x 10(6) cells/l, viral load is generally quite stable, although acute minor infections are associated with transient fluctuations generally lasting no more than 1 week.

Acquired Immunodeficiency Syndrome↗